P1619: LOME PILOT STUDY: A MULTICENTER CONTROLLED RANDOMIZED CLINICAL TRIAL OF LOW- VERSUS INTERMEDIATE-DOSE IMMUNE TOLERANCE INDUCTION WITH RECOMBINANT FACTOR VIII (OMFILOCTOCOG ALFA, SCT800) IN CHINA
Authors: Zengping LI, Runhui Wu
Journal: HemaSphere (2023)

Topic: 33. Bleeding disorders (congenital and acquired) Background: In China and other developing countries with economic constraint, low-dose (LD) ITI is economically more feasible and is therefore preferred. We previously reported that the LD-ITI (with or without IS) as used in China on severe hemophilia A (SHA) patients with high-risk-inhibitors [immediate pre-ITI inhibitor titer >10 Bethesda Units (BU)] achieved overall success rate equivalent to that using higher dose ITI in the I-ITI study, yet with an ~90% cost reduction. But there were limitations in that study, like the heterogeneity of patients between our center and I-ITI study, and the potential bias of retrospective study. Aims: Thus, we conducted a multicenter controlled randomized clinical study (RCT) comparing the efficacy, safety, and cost of LD-ITI vs intermediate-dose (MD) ITI in SHA children with inhibitors (ChiCTR2200056603). Here, we presented the efficacy results of polit study. Methods: Eligible criteria: (1) diagnosed with SHA; (2) peak historical titer was ≥5 BU and ≤ 200BU; (3) have not received ITI therapy; (4) age ≤8 years old. All patients were randomized into LD-ITI (rFVIII 50 IU/kg once every other day) or MD-ITI (rFVIII 100 IU/kg/day) group, and finished the follow-up of 24 months after ITI initiation from 4 hemophilia comprehensive care centers in China. The first participant was enrolled on March 2022. It is planned to recruit 30 participants within 12 months. ITI outcomes: (i) Success: negative inhibitor titer and FVIII recovery ≥66% of expected. (ii) Partial success: negative inhibitor titer, but with abnormal FVIII recovery. (iii) Failure: failure to achieve criterial of success or partial success. Results: Twenty-six patients were enrolled until February 2023. The patients’ baseline demographics and clinical characteristics between LD group and MD group were not significantly different (Data not shown). Until to the interim analysis, the median time of ITI treatment was 5.6 (minimum – maximum, 1.1 – 10.4) months. All patients are still in the process of 24-month ITI treatment. Therefore, ITI success/partial success rates were analyzed by treatment arm and time of ITI (Figure 1). With the extension of treatment time, the success/partial success rates were increasing. In MD group, all patients with ≥5 months of ITI treatment, achieved success. In LD group, 50% (1/2) of patients with ≥9 months of ITI treatment obtained success. None success patients relapsed (Figure 1). The time to ITI success was significantly shorter in MD group than in LD group (2.6 vs. 8.5 months, p =0.0015). Similarly, more quickly achieved ITI partial success in MD group (2 vs. 4.7 months, p <0.001) (Figure 1). Monthly bleeding rate (MBR, 0.2 vs. 0.9, p =0.02) and monthly joint bleeding rate (MJBR, 0.1 vs. 0.5, p =0.02) were both significantly higher in LD during phase 1 (from ITI initiation to partial success) of ITI (Data not shown). Summary/Conclusion: Compared with LD-ITI (with rFVIII), SHA children with high-titer inhibitors with MD-ITI (with rFVIII) obtained success/partial success more quickly and had less breakthrough bleedings within ITI period. The comparison of ITI success/partial success rates between MD-ITI and LD-ITI groups required longer ITI treatment time to evaluate.Keywords: Hemophilia A